Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lancet Oncol. 2022 Sep;23(9):1156-1166. doi: 10.1016/S1470-2045(22)00392-8. Epub 2022 Aug 4.
Few standard treatment options are available for patients with metastatic sarcomas. We did this trial to evaluate the efficacy, safety, and changes in the tumour microenvironment for durvalumab, an anti-PD-L1 drug, and tremelimumab, an anti-CTLA-4 drug, across multiple sarcoma subtypes.
In this single-centre phase 2 trial, done at The University of Texas MD Anderson Cancer Center (Houston, TX USA), patients aged 18 years or older with advanced or metastatic sarcoma with an Eastern Cooperative Oncology Group performance status of 0 or 1 who had received at least one previous line of systemic therapy were enrolled in disease subtype-specific groups (liposarcoma, leiomyosarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma, synovial sarcoma, osteosarcoma, alveolar soft-part sarcoma, chordoma, and other sarcomas). Patients received 1500 mg intravenous durvalumab and 75 mg intravenous tremelimumab for four cycles, followed by durvalumab alone every 4 weeks for up to 12 months. The primary endpoint was progression-free survival at 12 weeks in the intention-to-treat population (all patients who received at least one dose of treatment). Safety was also analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02815995, and is completed.
Between Aug 17, 2016, and April 9, 2018, 62 patients were enrolled, of whom 57 (92%) received treatment and were included in the intention-to-treat population. With a median follow-up of 37·2 months (IQR 1·8-10·1), progression-free survival at 12 weeks was 49% (95% CI 36-61). 21 grade 3-4 treatment-related adverse events were reported, the most common of which were increased lipase (four [7%] of 57 patients), colitis (three [5%] patients), and pneumonitis (three [5%] patients). Nine (16%) patients had a treatment related serious adverse event. One patient had grade 5 pneumonitis and colitis.
The combination of durvalumab and tremelimumab is an active treatment regimen for advanced or metastatic sarcoma and merits evaluation in specific subsets in future trials.
AstraZeneca.
转移性肉瘤患者的标准治疗选择有限。我们进行这项试验，以评估抗 PD-L1 药物 durvalumab 和抗 CTLA-4 药物 tremelimumab 在多种肉瘤亚型中的疗效、安全性和肿瘤微环境变化。
在这项由美国德克萨斯大学 MD 安德森癌症中心（休斯顿，美国）进行的单中心 2 期试验中，招募了年龄在 18 岁及以上、患有晚期或转移性肉瘤且东部合作肿瘤学组体能状态为 0 或 1 的患者，他们之前接受过至少一线系统治疗，并按照肉瘤亚型进行分组（脂肪肉瘤、平滑肌肉瘤、血管肉瘤、未分化多形性肉瘤、滑膜肉瘤、骨肉瘤、腺泡软组织肉瘤、脊索瘤和其他肉瘤）。患者接受静脉注射 durvalumab 1500 mg 和 tremelimumab 75 mg 共 4 个周期，随后单独使用 durvalumab 每 4 周 1 次，最多 12 个月。主要终点是意向治疗人群（至少接受过 1 剂治疗的所有患者）在 12 周时的无进展生存期。在意向治疗人群中还分析了安全性。该试验在 ClinicalTrials.gov 注册，NCT02815995，现已完成。
2016 年 8 月 17 日至 2018 年 4 月 9 日期间，共纳入 62 例患者，其中 57 例（92%）接受治疗并纳入意向治疗人群。中位随访 37.2 个月（IQR 1.8-10.1），12 周时的无进展生存期为 49%（95%CI 36-61）。报告了 21 例 3-4 级治疗相关不良事件，最常见的是脂肪酶升高（57 例患者中有 4 例[7%]）、结肠炎（3 例[5%]患者）和肺炎（3 例[5%]患者）。9 例（16%）患者发生与治疗相关的严重不良事件。1 例患者发生 5 级肺炎和结肠炎。
durvalumab 和 tremelimumab 联合治疗是晚期或转移性肉瘤的一种有效治疗方案，值得在未来的试验中对特定亚组进行评估。
阿斯利康。
